Estrogen receptor (ER) β modulates ERα responses to estrogens in the developing rat ventromedial nucleus of the hypothalamus

The mechanisms by which estradiol exerts specific actions on neural function are unclear. In brain the actions of estrogen receptor (ER) alpha are well documented, whereas the functions of ER beta are not yet fully elucidated. Here, we report that ER beta inhibits the activity of ER alpha in an anatomically specific manner within the neonatal (postnatal d 7) brain. Using selective agonists we demonstrate that the selective activation of ER alpha in the relative absence of ER beta activation induces progesterone receptor expression to a greater extent than estradiol alone in the ventromedial nucleus, but not the medial preoptic nucleus, despite high ER alpha expression. Selective activation of ER beta attenuates the ER alpha-mediated increase in progesterone receptor expression in the ventromedial nucleus but has no effect in medial preoptic nucleus. These results suggest that ER alpha/ER beta interactions may regulate the effects of estrogens on neural development and reveal the neonatal brain as a unique model in which to study the specificity of steroid-induced gene expression.